1. Field of the Invention
The present invention relates to new compounds having an aryl amine substituted quinoxaline and their use.
2. The Prior Arts
Overexpression of cancerous inhibitor of protein phosphatase 2A (abbreviated as CIP2A) has been found in several common human cancers including acute leukemia, prostate cancer, non-small cell lung cancer, gastric cancer, head or neck cancer, colon cancer and breast cancer and has been linked to clinical aggressiveness in tumors and promotion of the malignant growth of cancer cells. CIP2A interacts directly with the transcription factor c-Myc and inhibits the PP2A dephosphorylation of c-Myc, thereby stabilizing the oncogenic c-Myc from degradation.
Protein phosphatase 2A (abbreviated as PP2A) is a crucial regulator of cell proliferation by dephosphorylation of protein kinases on serine or threonine residues. PP2A is composed of three subunits which regulate substrate specificity, cellular localization and enzymatic activity. For example, PP2A dephosphorylates p-Akt at serine 473 and reduces the cell growth. Hence, the CIP2A-PP2A-Akt signaling cascade is thought to be an important survival regulator in cancers. In addition, SET has been found as another potent inhibitor of PP2A, and the expression of SET has been found in tumor tissues of different human malignant disease, the expression level of SET is closely correlated with cell growth rate.
Accordingly, it needs to develop a compound which is capable of antagonize SET or CIP2A repressing PP2A to reactive PP2A in cancer cells and subsequently reducing p-Akt cancer signal cascade to induce tumor cell apoptosis, the compound can be a new anticancer strategy.